Abstract

Telomere shorting occurs after repeated cell division and has a key role in cell senescence, differentiation, and immortalization. Thus, telomere maintenance is critical for cancer progression. Telomere length is mainly regulated by telomerase activity associated with transcriptional activity of human telomerase reverse transcriptase (hTERT), a subunit of telomerase. The dysregulation and reactivation of hTERT gene expression may play an important role in facilitating tumor development. The hTERT promoter region was well identified and is rich in transcription factor binding sites including c-myc, SP1, and esterogen. In our previous study, hTERT polymorphisms, rs2753940 (-1327C>T), rs2853669(-244 T>C), rs2736100 and MNS16A, were examined for lung cancer association study. To identity effect of the hTERT polymorphisms on telomere length and transcriptional activity, we determined telomere length according to hTERT polymorphisms. The two hTERT polymorphisms, rs2753940 (-1327C>T), rs2853669 (-244 T>C), have a significant association with telomere length (P = 0.04, P = 0.013, respectively). This telomere length may be determined by hTERT expression which was regulated promoter polymorphism (rs2853669) by changing of c-MYC binding. We evaluated that rs2853669 is significantly associated with lung cancer prognosis in NSCLCs. Two promoter SNPs have a role in expression of hTERT, which may affect telomere length. These two polymorphisms may be used for risk and prognostic marker of lung cancer.